Piperonal

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Data source

Reference

Reference Type:

publication

Title:

The Inhibition of Rat Nasal Cytochrome P-450-dependent mono-oxygenase by the Essence Heliotropin (Piperonal)

Author:

Dahl AR

Year:

1982

Bibliographic source:

Drug Metabolism and Disposition. 1982;10(5):553-554

Materials and methods

Objective of study:

other: Test for the ability of heliotropin to inhibit cytochrome P450-mediated oxidation reactions.

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The effects of heliotropin on cytochrome P450-mediated oxidative reactions were evaluated in vitro in rat nasal and liver microsomes.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Piperonal

EC Number:

204-409-7

EC Name:

Piperonal

Cas Number:

120-57-0

Molecular formula:

C8H6O3

IUPAC Name:

1,3-benzodioxole-5-carbaldehyde

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Heliotropin
- Analytical purity: 99%

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Lovelace Inhalation Toxicology Research Institute
- Age at study initiation: 12 to 16 weeks

Further details were not reported.

Administration / exposure

Route of administration:

other: in vitro

Vehicle:

other: A vehicle was used but its identity was not reported.

Details on exposure:

Heliotropin (3 mM) was incubated with nasal and liver microsomes for 30 minutes at 37°C to evaluate its possible effect on oxidative metabolism of methyl N-methylanthranilate (DMA). Further details were not reported.

Duration and frequency of treatment / exposure:

30 minute incubation period.

Doses / concentrations

Remarks:

Doses / Concentrations:
3 mM

No. of animals per sex per dose / concentration:

Not applicable

Control animals:

other: Not applicable

Positive control reference chemical:

Not applicable

Details on study design:

Heliotropin (3 mM) was incubated with nasal and liver microsomes for 30 minutes at 37°C to evaluate its possible effect on oxidative metabolism of methyl N-methylanthranilate (DMA). Further details were not reported.

Details on dosing and sampling:

No details provided.

Statistics:

Not required.

Results and discussion

Main ADME results

Type:

other: Inhibition

Results:

Heliotropin inhibited CYP450 activity in nasal, but not liver, microsomes.

Any other information on results incl. tables

Table 1: Percentage of DMA Metabolism in the Presence of Heliotropin Comapred to Control
Microsomes	Heliotropin
Nasal	23.1 ± 0*
Liver	83.6 ± 2.6
* Probability that rates are the same as control < 0.05 (N=2)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Heliotropin inhibited CYP450 activity in nasal but not liver microsomes.
Heliotropin inhibited CYP450 activity in nasal but not liver microsomes.

Executive summary:

This study demonstrated that incubation with heliotropin (3 mM) inhibited CYP450-mediated oxidative metabolism of methyl N-methylanthranilate by rat nasal microsomes. No such inhibition was observed in rat liver microsomes. These data suggest that heliotropin may exert an inhibitory effect on nasal, but not liver, CYP450-mediated oxidation reactions.